Nipple aspirate fluids from women with breast cancer contain increased levels of group IIa secretory phospholipase A2

Abstract

Arachidonic acid, a bioactive molecule metabolized into prostaglandins and leukotrienes, contributes to cellular proliferation and tumor progression. Group IIa secretory phospholipase A2 (sPLA2-IIa) can facilitate arachidonate release from cellular phospholipids, suggesting its involvement in tumor evolution. Analysis of breast nipple aspirate fluid (NAF), a noninvasive research tool, allows the identification of biomarkers of breast cancer. We sought to determine whether sPLA2-IIa expression might be related to breast cancer development or progression. sPLA2-IIa expression was evaluated in NAF samples from 110 women (57 women with and 53 without breast cancer) using ELISA and western blotting; ultrastructural immunolocalization was performed in epithelial cells floating in NAF. Immunocytochemistry revealed that sPLA2-IIa is a constitutive intracellular protein suggesting that breast ductal cells synthesize and secrete the 14 kDa protein in NAF. Among all 110 subjects, sPLA2-IIa expression was significantly increased both in NAF and within ductal epithelial cells from cancer containing breasts. While in healthy women menopausal status did not influence sPLA2-IIa expression (P = 0.457), among patients with breast cancer there was a significant down-regulation in postmenopausal subjects (P < 0.0001). Moreover, sPLA2-IIa concentration in NAF from breast cancer patients was positively correlated with tumor stage (r (2) = 0.979, P = 0.0012), suggesting an active secretion/accumulation of the enzyme in NAF based on tumor burden. sPLA2-IIa activity may serve a dual role in breast carcinogenesis, beneficial in its release of arachidonate and detrimental in the metabolic conversion of arachadonic acid into prostaglandins and leukotrienes.

Plasma phospholipase A2 activity may serve as a novel diagnostic biomarker for the diagnosis of breast cancer

“…Furthermore, Yamashita et al (22) did not identify an association between steroid hormone receptor status and the concentration of PLA2 in BC tissues. These results were also consistent with those produced by Mannello et al (12). However, induced abortion, oral contraceptive use, family history of BC, delayed child birth and reduced duration of breast feeding have been identified as risk factors based on previous studies.…”

“…In addition, certain modern imaging techniques, including breast molybdenum target mammography, produce false positive results, are expensive, inconvenient and require painful patient examinations (13,28). Early detection of BC has contributed to a 3% annual decline in patient mortality rate (12). Effect of exposure to secondhand smoke on PLA2 and sPLA2 activity.…”

“…These are: Cytosolic PLA2 (cPLA2), calcium-independent PLA2 (iPLA2), secreted PLA2 (sPLA2) and platelet activating factor acetyl hydrolases (11). It has been demonstrated that sPLA2-IIa, a secretory PLA2 enzyme, is highly expressed in certain human cells and tissues, and is associated with various diseases, including cancer (5,12).…”

Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival

“…The involvement of sPLA 2 s in breast cancer has not been studied, and there are only a few reports correlating the increased expression of group IIA sPLA 2 with advanced cancer and decreased patient survival [17,36]. The aim of this study was to determine whether hGX sPLA 2 affects breast cancer cell growth and survival, and to delineate the underlying mechanism of action.…”

Expression of secreted phospholipase A2-Group IIA correlates with prognosis of gastric adenocarcinoma

“…Studies of gastric adenocarcinoma have reached similar conclusions (36). Data from clinical studies suggests that sPLA2-II expression is a valuable prognostic indicator that may be applied to breast (37), esophageal (38), gastric (35), colon (39), liver (40) and pancreatic cancer (26). In clinical practice, high sPLA2-II levels may predict poor clinical outcomes; thus indicating the need for secondary screening of patients.…”